Summary of Work: Significant variations in the metabolism of various drugs and environmental chemicals which are metabolized via cytochrome P450 (CYP) enzymes exist between humans. Many of these interindividual variations are attributed to polymorphisms in the CYP2C subfamily of enzymes. Current work focused on investigating the functional significance of specifically bioengineered CYP enzymes towards the metabolism of various substrates. Most recent studies identified new defective alleles of CYP2C19. Assessment of the metabolisc activities of these alleles demonstrated that the CYP2C19*5 allele contributes to the poor metaboloizers phenotype towards S-mephyntoin and tolbutamide. Additionally, the recombinant of a second allele (CYP2C19*6) had negligible metabolic activity towards S-mephenytoin which is indicative that CYP2C19*6 represents a poor metabolizer allele as well. Thus, both CYP2C19*5 and CYP2C19*6 alleles contribute to the poor metabolizers phenotypes.